Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy.
Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P less than 0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P less than 0.01) and thymidine kinase activity (P less than 0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P less than 0.05) in the rats treated with cyclosporine as compared to the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
Kahn
D
D
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Gavaler
J S
JS
Lai
H
H
Makowka
L
L
Eagon
P K
PK
Francavilla
A
A
Starzl
T E
TE
Van Thiel
D H
DH
D000818:Animals; D003524:Cyclosporins / Q000633:toxicity*; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000187:drug effects*; D013268:Stimulation, Chemical; D013937:Thymidine Kinase / Q000378:metabolism
D003524:Cyclosporins; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013937:Thymidine Kinase; D009955:Ornithine Decarboxylase